SEARCH · PubMed Health

Results for “locus coeruleus”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

PubMed1980

Fine structure of rat locus coeruleus.

Locus coeruleus of the rat was studied in material prepared by aldehyde-osmium fixation. Cell bodies of locus coeruleus neurons possess large nuclei with a prominent nucleolus, a homogeneous karyoplasm of moderate density, and occasional indentations of the nuclear membrane. The cytoplasm is rich in organelles, including an extensive network of endoplasmic reticulum which forms well organized Nissl bodies. The highly developed Golgi apparatus surrounds the nucleus and extends into large dendritic trunks. In coronal section, cell bodies appear elongated along an approximate dorso-ventral axis, and most dendrites as well as axons appear in cross-section. In parasagittal sections the cells are very elongate, with dendrites and axons in the neuropil mostly cut longitudinally. Thus, locus coeruleus neurons possess disc-shaped dendritic fields parallel to the anterior-posterior axis of the brainstem, with predominantly longitudinal axo-dendritic synaptic configurations. Presynaptic profiles in locus coeruleus neuropil were classified according to the characteristics of their vesicle populations and other features. The most frequently encountered synaptic ending was characterized by small, round, densely packed synaptic vesicles, and comprised approximately 41% of the total sample of 775 synapses. Another group having large, rounded synaptic vesicles, which could be traced in a number of instances to large myelinated axons, accounted for 20% of the sample. Synaptic endings having large, flattened vesicles were also numerous, comprising 23% of the total. Another category of presynaptic endings was identified as those possessing numerous, small, flattened vesicles and comprising about 11% of the sample. Presynaptic endings having many vesicles of mixed sizes accounted for 2% of the total, and another group of the same proportion having small, rounded synaptic vesicles but also an unusually large number of larger, dense-cored vesicles was also present. Two other categories of synaptic endings were encountered, each comprising less than 1% of the total. One of these was derived from small, unmyelinated axons and contained clusters of pleomorphic synaptic vesicles. The other consisted of dendro-dendritic synapses between locus coeruleus neurons and also displayed small clusters of pleomorphic synaptic vesicles near the zone of synaptic apposition. Quantitative analysis revealed that most afferents to the nucleus synapse onto dendrites ranging between 0.5 and 2.5 micrometers in diameter and onto spine-like appendages derived from somata and dendrites. There were no significant differences between different categories of afferent terminals and their spatial distribution onto various postsynaptic targets of locus coeruleus neurons.

Animals↗

PubMed1994

Catecholaminergic systems in the zebrafish. I. Number, morphology, and histochemical characteristics of neurons in the locus coeruleus.

The locus coeruleus is a noradrenergic nucleus located in the isthmal tegmentum. In mammals, it contains several thousand neurons that have diverse projection patterns and contain various neuropeptides. In fishes, this nucleus contains few neurons. This study attempts to define and quantify morphological types of locus coeruleus neurons, and search for neurochemical subpopulations in the zebrafish. In this fish, the locus coeruleus contains between 3 and 10 neurons, and most nuclei contain between 5 and 8 cells. Nuclei in more inbred lines of fish have a narrower range of neurons. The difference in neuron number between the two sides of the same brain is small, but only 24% of the brains have identical numbers on both sides. These observations suggest that there is a two-step control of neuron number: the genetic constitution of the fish determines the approximate number of cells, while epigenetic factors determine the final number. Based on dendritic orientation, three types of cells are identified: (1) V type, neurons with only ventrally projecting dendrites; (2) L type, neurons with only laterally projecting dendrites; and (3) VL type, neurons with both ventrally and laterally projecting dendrites. Over 65% of the neurons are of the V type; some nuclei have V type cells only. There is a correlation between the total number of neurons and the ratio of each cell type. In nuclei with five cells or fewer, over 80% of the neurons are V type; higher percentages of the other two types are seen in nuclei with 6 or more neurons. The dendritic morphology and orientation suggest that various types of neurons may receive different inputs. Cholinesterases are not detectable in locus coeruleus neurons. Immunocytochemical staining for a number of neuropeptides also fails to demonstrate detectable levels. Neuropeptide Y is present in some cells abutting the locus coeruleus, but these are probably not catecholamine-containing neurons. Some neurons contain choline-acetyltransferase. These observations suggest that locus coeruleus neurons of the zebrafish may be morphologically and neurochemically heterogeneous.

Acetylcholinesterase↗

PubMed1983

Enhancement of learning four weeks after stimulation of the nucleus locus coeruleus in the rat: differential effects of dorsal noradrenergic bundle lesion and lesion of the locus coeruleus proper.

In previous studies we showed that electrical stimulation of the nucleus locus coeruleus produced, four weeks later, a significant improvement in performance in acquisition of food-reinforced operant conditioning. In the two experiments reported here, we tested the role of the dorsal noradrenergic bundle and of the locus coeruleus proper in this long-term effect. Lesioning the dorsal noradrenergic bundle did not have a clear and consistent effect, whereas lesion of the nucleus coeruleus proper suppressed almost totally the beneficial effect of the stimulation. In the first experiment, the dorsal noradrenergic bundle was lesioned by local bilateral injection of 6-hydroxydopamine, 8 days before stimulation of the locus coeruleus. Four weeks after the stimulation, the rats were tested for acquisition of the operant task. Three control groups were used: not lesioned but stimulated, lesioned but not stimulated, and not lesioned/not stimulated. The locus coeruleus stimulation produced the same improvement of performance at the beginning of the acquisition, whether or not the dorsal noradrenergic bundle had been lesioned. However, a significant decrement of performance was observed in lesioned and stimulated rats during the last 40 min of the acquisition. In the second experiment, the locus coeruleus proper was destroyed by bilateral local injection of 6-hydroxydopamine and the locus coeruleus region was stimulated 15 days later. Three control groups were used, as in the first experiment. All the rats were tested 4 weeks later for acquisition of the operant task. The locus coeruleus lesion significantly attenuated the beneficial effect of the stimulation; however, the performance of the lesioned and stimulated rats was still significantly superior to that of the lesioned but not stimulated rats. These results suggest that the noradrenergic locus coeruleus system is involved in the long-term effect, but that the rostral projections passing through the dorsal bundle, in front of the lesion, are not critically involved in the observed effect.

Animals↗

PubMed1994

Catecholaminergic systems in the zebrafish. II. Projection pathways and pattern of termination of the locus coeruleus.

The locus coeruleus is a widely projecting isthmal noradrenergic nucleus. In the zebrafish, it consists of between three and ten neurons, most of which have multiple, bilaterally projecting axons. Immunohodological studies show that the locus coeruleus provides most, if not all, of the noradrenergic innervation of the brain rostral to the isthmus. The pathways and targets in the zebrafish are similar to ascending coeruleal projections of other vertebrates. Axons ascend through two main pathways: the longitudinal catecholamine bundle and the periventricular catecholamine pathway. The former is a dense meshwork of varicosity-bearing axons which ascends along the lateral longitudinal fasciculus into the mesencephalon. In the posterior tuberal area, this bundle dives ventrally and assumes a lateral position. In the diencephalon, it takes up a position ventral to the medial forebrain bundle, and follows this bundle into the telencephalon, where it joins the medial olfactory tract to enter the olfactory bulb. The periventricular catecholamine pathway is a diffuse pathway consisting of thick, smooth axons. It is associated with the medial longitudinal fasciculus. Rostral to the nucleus of the medial longitudinal fasciculus, this pathway joins the longitudinal catecholamine bundle around the medial forebrain bundle. The periventricular pathway gives rise to coarse terminal arbors with large but sparse varicosities, whereas the longitudinal catecholamine bundle gives rise to terminal plexuses with fine and dense fibers and varicosities. Among the more densely innervated regions are the raphé nucleus, the interpeduncular nucleus, the torus semicircularis, parts of the hypothalamus, and the suprachiasmatic and preoptic areas. The torus longitudinalis, optic tectum, cerebellum, habenular complex, the dorsomedial zone of area dorsalis telencephali, and the olfactory bulb are moderately innervated. The nucleus glomerulosus, the torus lateralis and lateral subnuclei of the nucleus diffusus, and the anterior tuberal nucleus are devoid of noradrenergic innervation.

Animals↗

PubMed2002

Expression of mRNA and functional alpha(1)-adrenoceptors that suppress the GIRK conductance in adult rat locus coeruleus neurons.

1. Locus coeruleus neurons in adult rats express binding sites and mRNA for alpha(1)-adrenoceptors even though the depolarizing effect of alpha(1)-adrenoceptor agonists on neonatal neurons disappears during development. 2. In this study intracellular microelectrodes were used to record from locus coeruleus neurons in brain slices of adult rats and reverse transcription-polymerase chain reaction (RT - PCR) was used to investigate the mRNA expression of alpha(1)- and alpha(2)-adrenoceptors in juvenile and adult rats. 3. The alpha(1)-adrenoceptor agonist phenylephrine had no effect on the membrane conductance of locus coeruleus neurons (V(hold) -60 mV) but decreased the G protein coupled, inward rectifier potassium (GIRK) conductance induced by alpha(2)-adrenoceptor or mu-opioid agonists. The GIRK conductance induced by noradrenaline was increased in amplitude when alpha(1)-adrenoceptors were blocked with prazosin. 4. RT - PCR of total cellular RNA isolated from microdissected locus coeruleus tissue demonstrated strong mRNA expression of alpha(1a)-, alpha(1b)- and alpha(1d)-adrenoceptors in both juvenile and adult rats. However, only mRNA transcripts for the alpha(1b)-adrenoceptors were consistently detected in cytoplasmic samples taken from single locus coeruleus neurons of juvenile rats, suggesting that this subtype may be responsible for the physiological effects seen in juvenile rats. 5. Juvenile and adult locus coeruleus tissue expressed mRNA for the alpha(2a)- and alpha(2c)-adrenoceptors while the alpha(2b)-adrenoceptor was only weakly expressed in juveniles and was not detected in adults. 6. The results of this study show that alpha(1)-adrenoceptors expressed in adult locus coeruleus neurons function to suppress the GIRK conductance that is activated by mu-opioid and alpha(2)-adrenoceptors.

Action Potentials↗

PubMed1989

The effect of amygdala kindled seizures on locus coeruleus activity.

Locus coeruleus (LC) neuronal activity was recorded in anesthetized and in awake behaving rats during the production of amygdala afterdischarges (AD's) using kindling protocol. Both LC multiple and single unit discharges were temporally correlated with the appearance of AD's in the amygdala. Seizures were manifested in single unit activity as significant increases in firing rate. In awake animals, a bursting pattern of discharges was observed. We postulate that the observed changes in the LC activity pattern may have a modulatory role in the development of kindled seizures.

Action Potentials↗

PubMed1994

Disturbances in blood pressure homeostasis modify GABA release in the locus coeruleus.

The locus coeruleus (LC) of anaesthetized rats was superfused with artificial cerebrospinal fluid through a push-pull cannula and the release of the amino acids gamma-aminobutyric acid (GABA), taurine and arginine was determined in the superfusate. Increases in blood pressure (BP) induced either by intravenous infusions of noradrenaline and phenylephrine or by blood injection enhanced the release of GABA in the LC. Decreases in BP elicited by intravenous infusion of sodium nitroprusside or by haemorrhage decreased the GABA release rate. The BP changes did not influence the release rates of taurine and arginine. These findings demonstrate that GABA release in the LC is modified by cardiovascular impulses and suggest that GABAergic neurones modulate LC activity in response to disturbances in BP homeostasis.

Animals↗

PubMed1991

Mechanisms of opioid actions on neurons of the locus coeruleus.

The locus coeruleus (LC) has provided a useful model for pioneering studies of the mechanisms underlying the acute and chronic actions of opioid drugs. Acutely, opioids inhibit the electrical activity of single neurons in the rat and guinea pig LC. Inhibition is due to a membrane hyperpolarisation. In these cells, opioids act on mu-receptors to increase the opening of inwardly rectifying potassium channels, thus leading to hyperpolarisation. The mu-receptors are coupled to potassium channels via G-proteins which are sensitive to inactivation by pertussis toxin. This coupling process is quite direct, in that it does not involve freely diffusible intracellular second messengers. Agonists specific for other receptors, such as alpha 2- and somatostatin-receptors, are capable of opening the same population of potassium channels on LC neurons. Following chronic treatment of animals with morphine, a specific deficit develops in the ability of mu-receptors to open potassium channels, producing reduced sensitivity of LC neurons to inhibition by opioids.

Action Potentials↗

PubMed1991

Angiotensin II and the locus coeruleus.

The locus coeruleus (LC) is a putative site of action for angiotensin II in the brain. Immunocytochemical studies have identified angiotensin II-like immunoreactive material in nerve terminals innervating the LC, and the LC contains one of the highest densities of angiotensin II receptor binding sites in the rat brain. Recent studies using selective neurotoxins suggest that the binding sites for angiotensin II in the LC are present on noradrenergic perikarya. Angiotensin II receptors are now known to exist as two subtypes that are distinguishable both pharmacologically and biochemically. Radioligand binding studies using agonists and antagonists selective for these angiotensin II receptor subtypes indicate that the rat LC contains a mixture of the two known angiotensin II receptor subtypes, but that the PD123177-sensitive AII beta receptor subtype is predominant. Comparisons of spontaneously hypertensive rats with normotensive rats indicates that angiotensin II and its receptors in the LC are elevated in the hypertensive rat strain. Studies of the biochemical and physiological actions of angiotensin II in the LC have not yet established an agreed-upon function for angiotensin II in this nucleus.

Angiotensin II↗

PubMed1993

Differential regional hemodynamic changes produced by L-glutamate stimulation of the locus coeruleus.

The locus coeruleus (LC) exerts an inhibitory influence on the cardiovascular system. Microinjection of the excitatory amino acid, L-glutamate, into the LC elicits a decrease in arterial pressure as a result of a decrease in total peripheral resistance (TPR). The aim of the present study was to examine the role of the LC in the regulation of the regional hemodynamics. Employing anesthetized rats, the blood flow to the renal, mesenteric and hind-limb vascular beds was measured with an electromagnetic flowmeter. The changes in regional blood flow and vascular resistance evoked by chemical stimulation of the LC were examined separately in each region. During the depressor response elicited by LC stimulation, the hind-limb and renal vascular resistance was significantly decreased, while the mesenteric resistance was unchanged. The vasodilatation appeared to be more prominent in the hind-limb muscle than in the systemic circulation. Renal nerve denervation attenuated the decrease in renal vascular resistance elicited by LC stimulation. However, a small part of this response still remained in the denervated kidney. The present results suggest therefore that: (1) LC neurons exert differential hemodynamic effects on the hind-limb muscle, renal and mesenteric vascular beds; (2) the largest contribution to the decrease in TPR is related to vasodilatation in the hind-limb muscles; and (3) the renal vasodilation elicited by LC stimulation is not mediated solely by the renal innervation.

Animals↗

PubMed1999

Early postnatal alcohol exposure produced long-term deficits in brain weight, but not the number of neurons in the locus coeruleus.

The locus coeruleus (LC), a small nucleus in the pontine tegmentum with clusters of norepinephrine (NE) containing neurons, projects to more brain regions than any other nucleus in the central nervous system. Therefore, any neuroanatomical deficits in the LC may have wide-ranging functional implications. Previous studies have shown that heavy alcohol exposure during development can damage several brain regions receiving extensive innervation from the LC (e.g., cerebellum and olfactory bulb). In this study, we examined the effects of early alcohol exposure during development on neuronal numbers in the LC of the adult rat. Sprague-Dawley rat pups were reared using artificial rearing techniques during the brain growth spurt period (part of the third trimester equivalent). The pups in the alcohol group received 4.5 g/kg per day in two of their 12 daily feedings from postnatal days (PDs) 4-9. Gastrostomy and suckle control groups were also included. On PD 90, the animals were sacrificed and their brains were processed for stereological cell counting. Whole brain weight, the number of neurons in the LC, the volume and neuronal density of the LC were assessed. There was a significant reduction in whole brain weight of the alcohol group compared with that of the gastrostomy control group, demonstrating a long lasting effect of alcohol on overall brain growth. Nevertheless, there were no differences in neuronal number, density and volume of the LC between alcohol and gastrostomy groups. Results were discussed in relation to the issues of temporal and regional vulnerabilities.

Animals↗

PubMed1998

Morphological substrates underlying opioid, epinephrine and gamma-aminobutyric acid inhibitory actions in the rat locus coeruleus.

The locus coeruleus (LC) has been implicated in attentional processes related to orienting behaviors, learning and memory, anxiety, stress, the sleep-wake cycle, and autonomic control, as well as to contributing to the affective state. Direct activation of LC neurons causes desynchronization of the electroencephalogram, suggesting that the LC is an important modulator of the behavioral state. The LC has been an intensely studied neuronal system, as the physiology and pharmacology of this nucleus is well understood. This is mainly because of the similarity in neurochemical composition of LC cells which all contain norepinephrine in the rat. However, the homogeneity in neurotransmitter content in LC neurons is sharply contrasted by the heterogeneity of neurochemicals found in its afferent processes. Among these are axon terminals that contain inhibitory and excitatory amino acids, monoamines, and neuropeptides, many of which have been shown to exert differential physiological effects on LC discharge activity. Although much attention has focused on physiological activation of LC neurons, substantial evidence indicates that diverse afferents prominently inhibit noradrenergic cellular activity. Such inhibitory neurochemicals, which arise from local and extrinsic sources, include gamma-aminobutyric acid (GABA) and epinephrine as well as the neuropeptides methionine5-enkephalin and leucine5-enkephalin. Inhibitory transmission in the LC has widespread implications for norepinephrine release at diverse postsynaptic targets, and clinically useful pharmacological agents such as clonidine, an alpha2 adrenergic receptor agonist that potently inhibits the firing of LC neurons, alleviate some negative physical symptoms observed following withdrawal from opiates. In the present review, the synaptic and functional organization of selected inhibitory-type neurotransmitters in the LC obtained from immunoelectron microscopic data will be discussed.

Animals↗

PubMed2005

Single and repeated immobilization stress differentially trigger induction and phosphorylation of several transcription factors and mitogen-activated protein kinases in the rat locus coeruleus.

The locus coeruleus (LC) is a critical stress-responsive location that mediates many of the responses to stress. We used immunoblotting and immunohistochemistry to investigate changes in induction and phosphorylation of several transcription factors and kinases in the LC that may mediate the stress-triggered induction of tyrosine hydroxylase (TH) transcription. Rats were exposed to single or repeated immobilization stress (IMO) for brief (5 min), intermediate (30 min) or sustained (2 h) duration. Single IMO elicited rapid induction of c-Fos and phosphorylation of cyclic AMP response element-binding protein (CREB) without changing the expression of early growth response (Egr)1, Fos-related antigen (Fra)-2 or phosphorylated activating transcription factor-2. Repeated IMO triggered increased phosphorylation and levels of CREB along with transient induction of c-Fos and increased Fra-2 expression. Several mitogen-activated protein kinases were activated by repeated IMO, shown by increased phosphorylation of p38, c-Jun N-terminal kinase (JNK)1/2/3 and extracellular signal-regulated kinase (ERK1/2). ERK1 was the major isoform expressed, and ERK2 the predominant isoform phosphorylated. Repeated IMO elicited hyperphosphorylation of ERK1/2 selectively in TH immunoreactive neurons, with substantial nuclear localization. These distinct alterations in transcriptional pathways following repeated compared with single stress may be involved in mediating long-lasting neuronal remodeling and are implicated in the mechanisms by which acute beneficial responses to stress are converted into prolonged adaptive or maladaptive responses.

Animals↗

PubMed1994

Radioautographic evidence that the GABAA receptor antagonist SR 95531 is a substrate inhibitor of MAO-A in the rat and human locus coeruleus.

The locus coeruleus (LC), a major noradrenergic nucleus in the brain, probably has a functional role in the regulation of anxiety states as well as vigilance, attention, learning and memory. LC neurons are under the inhibitory control of gamma-aminobutyric acid (GABA) via ionotropic GABAA receptors. However, to date, little is known of the receptor binding characteristics of these neurons. In the present investigation we therefore examined by receptor radioautography the localization of the binding sites for different components of the GABAA receptor complex in the rat and human LC. Both rat and human LC neurons have a high density of binding sites for the pyridazinyl-GABA derivative [3H]SR 95531 (gabazine, a GABAA receptor antagonist for low affinity GABA recognition sites). However, at the concentrations used, no binding sites in the LC were detectable for the benzodiazepine receptor antagonist [3H]flumazenil, the GABAA receptor agonist (for high affinity sites) [3H]muscimol or the ionophore ligand [35S]t-butyl bicyclophosphorothionate (TBPS). Unexpectedly, the pharmacological specificity of [3H]SR 95531 binding to the LC differed markedly from that to most brain regions (IC50 values for GABA and RU 5135 respectively in the LC were > 10(-2) and 10(-3) M; and, for example, in the dentate gyrus the most labelled structure after the LC, 8 x 10(-7) and 1.8 x 10(-9) M). These differences prompted the further characterization of [3H]SR 95531 binding in the LC, revealing a significant affinity for monoamine oxidase type A (MAO-A), which is highly concentrated in this nucleus. In a competition binding study, a reduction of up to 25% of the [3H]SR 95531 binding was observed with MAO-A but not MAO-B inhibitors, at concentrations which produce maximum but selective enzyme inhibition. Correspondingly, 2 h after the oral administration of supramaximal doses of the MAO-A inhibitors moclobemide and Ro 41-1049 (but not the MAO-B inhibitor lazabemide) the in vitro binding of [3H]SR 95531 was markedly reduced (by 77 and 82% of controls respectively). Moreover, enzyme radioautography with [3H]Ro 41-1049 revealed that SR 95531 has a significant affinity for MAO-A (IC50 values were 10(-5) and 4 x 10(-6) M in the LC and dentate gyrus respectively) but not for MAO-B ([3H]lazabemide binding). Altogether, these findings suggest that the high-affinity binding of [3H]SR 95531 to the LC mainly reflects its affinity for MAO-A, which questions its utility as a selective ligand for low-affinity GABA recognition sites in the CNS.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1979

Studies on the dense-core vesicles in the ontogenesis of locus coeruleus. III. Statistical reconstruction of the diameter distribution of the dense-core vesicles in locus coeruleus during rat ontogenesis.

The method for statistical reconstruction of the diameters of dence-core vesicles, described in the previous work, is applied for studying the changes of these vesicles in the perikarya, the axonal boutons and the neuropile of the rat locus coeruleus during ontogenesis. The data obtained show the presence of the population during the embryonal development and of two populations of dense-core vesicles after birth in the structures studied. This finding is interpreted in connection with the different function of the dense-core vesicles and of the transmitters, respectively, in the development and function of the main noradrenergic nucleus in the brain of mammals -- locus coeruleus.

Age Factors↗

PubMed1978

Studies on the dense-core vesicles in the ontogenesis of locus coeruleus. I. Localization, type and density of the dense-core vesicles in locus coeruleus during rat ontogenesis.

In an attempt to clarify the function of dense-core vesicles quantitative estimation is made of their density and localization in the perikarya, axonal boutons and neuropil of rat locus coeruleus during different ontogenetic stages. The results obtained, compared with the fluorescence- and electronmicroscopic data, suggest participation of the dense-core vesicles in the neuronal development and differentiation: presence in the earliest embryonal periods, statistically significant increase in the density in the period of most intensified growth and maturing of the neuropil and axonal boutons, and change in the density of the perikarya in connection with intensified axonal transport. Quantitative data are also presented about the participation of the dense-core vesicles in synaptic transmission.

Animals↗

PubMed1991

Effects of locus coeruleus lesions on parkinsonian signs, striatal dopamine and substantia nigra cell loss after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in monkeys: a possible role for the locus coeruleus in the progression of Parkinson's disease.

Six pairs of female squirrel monkeys were given a daily intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 9-14 days, beginning the same day on which they received either a bilateral 6-hydroxydopamine lesion or a sham lesion of the locus coeruleus. Sham animals developed typical parkinsonian signs (i.e. tremor, bradykinesia, hypokinesia and reduced blink rate) which largely recovered by six to nine weeks after the start of MPTP treatment. At nine weeks, post mortem levels of striatal dopamine in these same animals were partially reduced (by 45%), and this only in the putamen, compared to values obtained from three non-operated, normal control animals. Additionally, histological examination revealed a moderate loss of neuronal cell bodies in the substantia nigra, pars compacta. In marked contrast, the locus coeruleus-lesioned monkeys exhibited little or no recovery from the parkinsonian signs induced by MPTP. Post mortem examination of these animals revealed profound decreases in caudate (by 84%) and putamen (by 91%) dopamine content, and severe neuronal cell loss in the substantia nigra pars compacta of all animals. These neurological, biochemical and histological assessments indicate that lesioning of the locus coeruleus impairs the recovery which usually occurs from the parkinsonian manifestations induced by MPTP in squirrel monkeys. The results support the hypothesis that deficient locus coeruleus noradrenergic mechanisms underlie the progression of Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1994

Regulation of expression of cAMP response element-binding protein in the locus coeruleus in vivo and in a locus coeruleus-like cell line in vitro.

Expression of the cAMP response element (CRE)-binding protein (CREB) has been thought to be constitutive and not subject to regulation. In the course of investigating effects of chronic morphine on the cAMP pathway in the locus coeruleus, a brain region important for opiate addiction, we found that levels of CREB immunoreactivity and CRE binding were increased by chronic morphine administration. To further investigate possible mechanisms underlying this unexpected finding, we studied the regulation of CREB expression in a cell line (CATH.a) that exhibits many properties of locus coeruleus neurons. Agents that activate the cAMP pathway led to a > 60% decrease in CREB mRNA in this cell line. Moreover, these alterations in CREB mRNA levels were associated with changes in levels of CREB immunoreactivity and CRE-binding activity. In contrast, the same treatments fail to alter CREB expression in PC12 pheochromocytoma cells.

Animals↗